title: Long pentraxin PTX3 attenuates ischemia reperfusion injury in a cardiac transplantation model.
abstract: Ischemia reperfusion (IR) injury is a major issue in cardiac transplantation, and inflammatory processes play a major role in myocardial IR injury. Long pentraxin-3 (PTX3) is a member of a phylogenetically conserved group of acute-phase reactants that are involved in inflammation and innate immunity. In our study, hearts of C57Bl/6 mice were flushed and stored in cold Bretschneider solution for 8 h and then transplanted into syngeneic recipient. We found that both mRNA and protein levels of PTX3 were increased following myocardial IR injury; neutralizing antibody against PTX3 aggravated cardiomyocyte apoptosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24 h after myocardial IR injury was reduced by exogenous PTX3 administration and increased by PTX3 neutralization in comparison with control. Cardiac output at 60 mmHg of afterload pressure was also increased in hearts with exogenous PTX3 administration and decreased with PTX3 neutralization (PTX3: 58.4 ± 7.4 ml/min;
  
  
  METHODS
  24.5 ± 3.8 ml/min; Anti-PTX3: 11.6 ± 1.7 ml/min; P < 0.05). Furthermore, PTX3 restricted expansion of γδ T cell that was the major source of IL-17A and down-regulated expression of IL-23 and IL-17A. In conclusion, PTX3 played a protective role in cardiomyocyte IR injury. PTX3 ameliorated cardiomyocyte apoptosis and infiltration of neutrophil and macrophage and then improved hemodynamic performance. This was associated with restricted γδ T-cell expansion and decreased IL-23/IL-17A expression.
authors.affiliation: Department of Anesthesiology and The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Zhu
authors.forename: Dan
authors.initials: D
authors.lastname: Cui
authors.forename: Kebin
authors.initials: K
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.forename: Jinjie
authors.initials: J
authors.lastname: Li
mesh_terms: D000209:Acute-Phase Proteins; D000818:Animals; D017209:Apoptosis; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D015536:Down-Regulation; D016027:Heart Transplantation; D020381:Interleukin-17 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D020556:Neutrophil Infiltration; D000683:Serum Amyloid P-Component / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D000099153:Pentraxins
chemical_list: D000209:Acute-Phase Proteins; D002097:C-Reactive Protein; D020381:Interleukin-17; D053759:Interleukin-23; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C098680:Il17a protein, mouse
keywords: IL-23/IL-17A; ischemia reperfusion injury; pentraxin-3; γδ T cell